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Structural study of a VirB4 homolog present in the type IV secretion system of Staphylococcus aureus.

Grant number: 24/03003-5
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Start date: June 01, 2024
End date: May 31, 2025
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal Investigator:Cristiane Rodrigues Guzzo Carvalho
Grantee:Laura Lúcia de Oliveira Santos
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Staphylococcus aureus is a Gram-positive bacterium with high pathogenicity in humans, capable of causing severe infections such as pneumonia and sepsis. Additionally, its ability to acquire antibiotic resistance and produce virulent toxins has made it a threat to modern public health. In light of this, an in-depth study of the type IV secretion system (T4SS), machinery that plays a crucial role in gene transfer, particularly in the context of antibiotic resistance via conjugation, may be essential for unraveling the underlying mechanisms of these infections. The objective of this project is to study the proteins encoded by the trsD and trsE genes, found in the pGO1 plasmid of Staphylococcus aureus, which together encode an ATPase homologous to the VirB4 protein present in the T4SS of Gram-negative bacteria. We intend to amplify, clone, and perform heterologous expression of these genes in Escherichia coli (E. coli), which will serve as a starting point for future structural analyses by crystallography.We aim to fill a knowledge gap, as the structural study of this complex in Gram-positive bacteria, such as S. aureus, is relatively scarce. The results of this study could contribute to a better understanding of the structural and functional characteristics of the T4SS and its potential impact on the pathogenicity of S. aureus.

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